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AIMS: To assess electroconvulsive therapy (ECT) outcomes in patients affected by depressive symptoms with versus without additional comorbid personality disorders/traits. METHODS: We identified observational studies investigating ECT clinical outcomes in patients affected by depressive symptoms with versus without comorbid personality disorders/traits in Embase/Medline in 11/2022. Our protocol was registered with PROSPERO (CRD42023390833). Study quality was evaluated using the Newcastle-Ottawa-Scale. Our primary outcomes were ECT response and remission rates. Meta-regression analyses included effects of in/outpatient percentages, age, number of ECT sessions, and electrode placement; subgroup analyses included the assessment methods for personality disorders/traits. We performed sensitivity analyses after excluding poor-quality studies. RESULTS: A total of 20 studies (n = 11,390) were included in our analysis. Patients with comorbid personality disorders/traits had lower remission rates (OR = 0.42, 95% CI = 0.31, 0.58, p < 0.001) with substantial heterogeneity (I2 = 93.0%) as well as lower response rates (OR = 0.35, 95% CI = 0.24, 0.51, n = 5129, p < 0.001) with substantial heterogeneity (I2 = 93.0%) compared with patients without comorbid personality disorders/traits. Relapse rates were higher in patients with versus without comorbid personality disorders/traits (OR = 3.23, 95% CI = 1.40, 7.45, k = 4, n = 239, p = 0.006) with moderate heterogeneity (I2 = 75.0%) and post-ECT memory impairment was more frequent in patients with versus without comorbid personality disorders/traits (OR = 1.41, 95% CI = 1.36, 1.46, k = 4, n = 471, p < 0.001) with minimal heterogeneity (I2 = 0.0%). Dropout rates were higher in patients with versus without comorbid personality disorders/traits (OR = 1.58, 95% CI = 1.13, 2.21, k = 3, n = 6145, p = 0.008). CONCLUSIONS: Patients with comorbid personality disorders/traits treated with ECT are reported to have lower response and remission rates and higher rates of side effects and relapse rates compared with patients without personality disorders/traits.
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Terapia Electroconvulsiva , Humanos , Terapia Electroconvulsiva/métodos , Depresión/terapia , Resultado del Tratamiento , Trastornos de la Personalidad/epidemiología , Trastornos de la Personalidad/terapia , RecurrenciaRESUMEN
Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder with a broad spectrum of motor and non-motor symptoms. The neuropathological characteristics of idiopathic PD are the degeneration of dopaminergic neurons in the striatum, and the propagation of aggregates of misfolded α-synuclein in the brain following a specific pattern (Braak et al., 2006). The relationship of this pattern with motor and cognitive symptoms is still equivocal. Therefore, we investigated longitudinally the spatio-temporal patterns of atrophy propagation in PD, their inter-individual variability and associations with clinical symptoms. Magnetic resonance (MR) images of 37 PD patients and 27 controls were acquired at up to 15 time-points per subject, and over observation periods of up to 8.8 years (mean: 3.7 years). MR images were analyzed by Deformation-based Morphometry to measure region volumes and their longitudinal changes. Differences of these regional volume data between patients and controls and their associations with clinical symptoms were calculated. At baseline, group differences in the regional volumes were found mainly in areas of the sensory, motor and orbitofrontal cortices, areas in the frontal operculum, inferior frontal sulcus, hippocampus and entorhinal cortex, and in the substantia nigra, among others. The longitudinal analysis yielded more widespread and more pronounced group differences, with significantly accelerated volume decreases in PD patients in the occipital and temporal lobes, the inferior parietal lobule, as well as in the insula, putamen and nucleus basalis Meynert. The white matter was less affected than the gray matter. Worse clinical scores (MMSE, PDQ-39, UPDRS-III) were in particular associated with volume decreases of cortical areas, amygdala and basal forebrain nuclei, but not of the basal ganglia. The observed longitudinal patterns of accelerated volume decrease in PD patients largely coincide with the pattern of α-synuclein pathology in PD stages 3-5 as proposed by Braak and colleagues. Thus, longitudinal DBM appears to depict already in-vivo the progression of neuropathological changes.
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Enfermedades del Sistema Nervioso , Enfermedad de Parkinson , Atrofia/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , alfa-SinucleínaRESUMEN
BACKGROUND AND PURPOSE: Patients with a corticobasal syndrome (CBS) present a rare form of atypical parkinsonism characterized by asymmetric clinical symptoms and progressive motor and nonmotor impairment, such as apraxia, alien limb phenomenon, aphasia, myoclonus, dystonia, and cognitive impairment. At early stages, clinical differentiation between CBS and idiopathic Parkinson's disease (IPD) can be challenging. METHODS: Using high-resolution T1-weighted images and voxel-based morphometry (VBM), we sought to identify disease-specific patterns of brain atrophy in a small sample of CBS and IPD patients at early stages of disease. We acquired MR images of 17 patients diagnosed with CBS and compared them with MR images of 17 subjects affected by IPD. Images were preprocessed and analyzed using VBM. RESULTS: When compared to each other, the CBS and IPD patients of our cohort showed differences in regional gray and white matter volume depending on the diagnosis, specifically in the superior longitudinal fascicle. CONCLUSIONS: In our small patients' group, VBM was able to detect changes in regional gray and white matter volume between patients affected by CBS and patients with IPD as early as 1.5-2 years after the onset of the first motor symptoms.
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Degeneración Corticobasal , Enfermedad de Parkinson , Trastornos Parkinsonianos , Atrofia/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Humanos , Imagen por Resonancia Magnética , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Trastornos Parkinsonianos/diagnóstico por imagenRESUMEN
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder clinically characterized by muscle atrophy and progressive paralysis. In addition to the classical ALS affecting both the upper and lower motoneurons (UMN and LMN), other subtypes with the predominant (or even exclusive) affection of the UMN or LMN have been identified. This work sought to detect specific patterns of cortical brain atrophy in the UMN and LMN phenotypes to distinguish these two forms from the healthy state. METHODS: Using high-resolution structural MRI and cortical thickness analysis, 38 patients with a diagnosis of ALS and predominance of either the UMN (n = 20) or the LMN (n = 18) phenotype were investigated. RESULTS: Significant cortical thinning in the temporal lobe was found in both the ALS groups. Additionally, UMN patients displayed a significant thinning of the cortical thickness in the pre- and postcentral gyrus, as well as the paracentral lobule. By applying multivariate analyses based on the cortical thicknesses of 34 brain regions, ALS patients with either a predominant UMN or LMN phenotype were distinguished from healthy controls with an accuracy of 94% and UMN from LMN patients with an accuracy of 75%. CONCLUSIONS: These findings support previous hypothesis that neural degeneration in ALS is not confined to the sole motor regions. In addition, the amount of cortical thinning in the temporal lobe helps to distinguish ALS patients from healthy controls, that is, to support or discourage the diagnosis of ALS, while the cortical thickness of the precentral gyrus specifically helps to distinguish the UMN from the LMN phenotype.
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BACKGROUND: A reliable measure of PSP-specific midbrain atrophy, the midbrain-to-pons ratio (MTPR) has been reported to support the differential diagnosis of progressive supranuclear palsy (PSP) from idiopathic Parkinson's disease (IPD). Since longitudinal analyses are lacking so far, the present study aimed to evaluate the diagnostic value of the relative change of MTPR (relΔt_MTPR) over a 1-year period in patients with PSP, IPD, and healthy controls (HC). METHODS: Midsagittal individual MRIs of patients with PSP (n = 15), IPD (n = 15), and healthy controls (HC; n = 15) were assessed and the MTPR at baseline and after 1 year were defined. The diagnostic accuracy of the MTPR and its relative change were evaluated using ROC curve analyses. RESULTS: PSP-patients had a significantly lower MTPR at baseline (M = 0.45 ± 0.06), compared to both non-PSP groups (F (2, 41) = 62.82, p < 0.001), with an overall predictive accuracy of 95.6% for an MTPR ≤ 0.54. PSP-patients also presented a significantly stronger 1-year decline in MTPR compared to IPD (p < 0.001). Though predictive accuracy of relΔt_MTPR for PSP (M = - 4.74% ± 4.48) from IPD (M = + 1.29 ± 3.77) was good (76.6%), ROC analysis did not reveal a significant improvement of diagnostic accuracy by combining the MTPR and relΔt_MTPR (p = 0.670). Still, specificity for PSP increased, though not significantly (p = 0.500). CONCLUSION: The present results indicate that the relΔt_MTPR is a potentially useful tool to support the differential diagnosis of PSP from IPD. For its relative 1-year change, still, more evaluation is needed.
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Enfermedad de Parkinson , Parálisis Supranuclear Progresiva , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Mesencéfalo/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Puente , Parálisis Supranuclear Progresiva/diagnóstico por imagenRESUMEN
An increasing number of neuroimaging studies addressing patients with corticobasal syndrome use macroscopic definitions of brain regions. As a closer link to functionally relevant units, we aimed at identifying magnetic resonance-based atrophy patterns in regions defined by probability maps of cortical microstructure. For this purpose, three analyses were conducted: (1) Whole-brain cortical thickness was compared between 36 patients with corticobasal syndrome and 24 controls. A pattern of pericentral atrophy was found, covering primary motor area 4, premotor area 6, and primary somatosensory areas 1, 2, and 3a. Within the central region, only area 3b was without atrophy. (2) In 18 patients, longitudinal measures with follow-ups of up to 59 months (mean 21.3 ± 15.4) were analyzed. Areas 1, 2, and 6 showed significantly faster atrophy rates than primary somatosensory area 3b. (3) In an individual autopsy case, longitudinal in vivo morphometry and postmortem pathohistology were conducted. The rate of magnetic resonance-based atrophy was significantly correlated with tufted-astrocyte load in those cytoarchitectonically defined regions also seen in the group study, with area 3b being selectively unaffected.
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Imagen por Resonancia Magnética , Enfermedades Neurodegenerativas/patología , Enfermedad de Parkinson/patología , Corteza Somatosensorial/diagnóstico por imagen , Corteza Somatosensorial/patología , Anciano , Astrocitos/patología , Atrofia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Corteza Somatosensorial/citología , SíndromeRESUMEN
BACKGROUND: Recently, therapeutic attempts to control motor choreatic hyperkinesia of Huntington's disease (HD) by means of pallidal deep brain stimulation (Gp-DBS) were successful. With respect to the clinical effects of Gp-DBS in juvenile hypokinetic-rigid HD (jHD; Westphal variant), only one single-case has been reported up to date. Oscillatory patterns of the Gp in jHD are not known. OBJECTIVES AND METHODS: This work aimed to analyse pallidal local field potential oscillations (LFP) in two patients with jHD treated with Gp-DBS. Safety data and clinical scores up to 12 months after DBS-electrode implantation were collected in the framework of a prospective trial (ClinicalTrials.gov; NCT00902889). RESULTS: Intraoperative LFP revealed local alpha and beta oscillations similar to those found in other movement disorders with akinetic rigid and dystonic presentation. Significant motor improvement was not found. There were no treatment-related complications or unresolved long-term adverse events. CONCLUSIONS: In spite of similar intraoperative LFP patterns of jHD with those of movement disorders benefitting from DBS, clinical results were not convincing in our patients, so that Gp-DBS in jHD cannot be generally recommended.
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Ondas Encefálicas/fisiología , Estimulación Encefálica Profunda/métodos , Globo Pálido/fisiología , Enfermedad de Huntington/fisiopatología , Enfermedad de Huntington/terapia , Adulto , Electrodos Implantados , Electroencefalografía , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Imagen por Resonancia Magnética , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the striatal presynaptic dopamine transporter (FP-CIT-SPECT) and postsynaptic D2 receptor (IBZM-SPECT) binding in patients with corticobasal syndrome (CBS). BACKGROUND: FP-CIT and IBZM are commercially available and approved SPECT tracers for in vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration, but only few data for CBS are available. METHODS: 23 patients meeting clinical criteria for early- to mid-stage CBS (disease duration ≤4 years) were examined with SPECT radiotracers FP-CIT and IBZM. All suspected CBS patients underwent a clinical follow-up examination and were re-evaluated after 19.7 ± 15.2 months (mean ± SD). Postmortem diagnosis was available for 2 patients. In patients who met research criteria for probable CBS at the final follow-up visit (n = 19; disease duration: 1.95 ± 0.91 years), SPECT binding values were compared to those of age- and gender-matched Parkinson's disease (PD) patients (n = 18, disease duration: 1.92 ± 0.91 years; clinical follow-up: 32 ± 29.6 months) and neurologically normal control subjects (n = 19). RESULTS: In comparison to the healthy control subjects, both patient groups showed significant and asymmetric reduction of the striatal presynaptic dopamine transporter binding, but PD patients had significantly lower FP-CIT binding ratios than probable-CBS patients. FP-CIT binding values of probable-CBS patients and healthy controls demonstrated marked overlaps, and in 7 patients (39%) scans revealed no dopaminergic deficit. IBZM uptake did not show significant between-group differences. CONCLUSION: Our data indicate that in the early- to mid-stage CBS the degree of nigrostriatal impairment is only mild with a significant proportion of preserved dopamine transporter binding.
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Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/metabolismo , Receptores de Dopamina D2/metabolismo , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano , Benzamidas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Trastornos Parkinsonianos/complicaciones , Pirrolidinas , TropanosRESUMEN
BACKGROUND: Movement disorders in Huntington's disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial. METHODS: In a controlled double-blind phase six patients (four chorea-dominant, two Westphal-variant) with predominant movement disorder were randomly assigned to either the sequence of 6-week internal- or 6-week external-pallidal stimulation, or vice versa, followed by further 3 months chronic pallidal stimulation at the target with best effect-side-effect ratio. Primary endpoints were changes in the Unified Huntington's Disease Rating Scale motor-score, chorea subscore, and total motor-score 4 (blinded-video ratings), comparing internal- versus external-pallidal stimulation, and 6 months versus baseline. Secondary endpoints assessed scores on dystonia, hypokinesia, cognition, mood, functionality/disability, and quality-of-life. RESULTS: Intention-to-treat analysis of all patients (n = 3 in each treatment sequence): Both targets were equal in terms of efficacy. Chorea subscores decreased significantly over 6 months (-5.3 (60.2%), p = 0.037). Effects on dystonia were not significant over the group due to it consisting of three responders (>50% improvement) and three non-responders. Westphal patients did not improve. Cognition was stable. Mood and some functionality/disability and quality-of-life scores improved significantly. Eight adverse events and two additional serious adverse events - mostly internal-pallidal stimulation-related - resolved without sequalae. No procedure-related complications occurred. CONCLUSION: Pallidal deep brain stimulation was demonstrated to be a safe treatment option for the reduction of chorea in Huntington's disease. Their effects on chorea and dystonia and on quality-of-life should be examined in larger controlled trials.
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Primary dissociated brain tissue from rodents is widely used in a variety of different scientific methods to investigate cellular processes in vitro. Often, for this purpose cell cultures need to be generated just on time, requiring extensive animal lab infrastructure. We show here that cryopreservation and thawing of dissociated tissue from rat cerebral cortex at embryonic day 18 is feasible without affecting its ability to form functional neuronal networks in vitro. Vitality of fresh and re-thawed cortical cells was comparable, assessed by CellTiter-Blue-assay, CytoTox-ONE assay, immunocytochemical characterization and in vitro neuronal network activity recordings on microelectrode arrays. These findings suggest that planning and execution of experiments might be considerably facilitated by using cryo-preserved neurons instead of acutely dissociated neural cultures due to fewer logistical issues with regard to animal breeding and pregnancy timed preparations.
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BACKGROUND: Corticobasal Syndrome (CBS) is a rare neurodegenerative syndrome characterized by unilaterally beginning frontoparietal and basal ganglia atrophy. The study aimed to prove the hypothesis that there are differences in hemispheric susceptibility to disease-related changes. METHODS: Two groups of CBS patients with symptoms starting either on the left or right body side were investigated. Groups consisted of four patients each and were matched for sex, age and disease duration. Patient groups and a group of eight healthy age-matched controls were analyzed using deformation field morphometry and neuropsychological testing. To further characterize individual disease progression regarding brain atrophy and neuropsychological performance, two female, disease duration-matched patients differing in initially impaired body side were followed over six months. RESULTS: A distinct pattern of neural atrophy and neuropsychological performance was revealed for both CBS: Patients with initial right-sided impairment (r-CBS) revealed atrophy predominantly in frontoparietal areas and showed, except from apraxia, no other cognitive deficits. In contrast, patients with impairment of the left body side (l-CBS) revealed more widespread atrophy, extending from frontoparietal to orbitofrontal and temporal regions; and apraxia, perceptional and memory deficits could be found. A similar pattern of morphological and neuropsychological differences was found for the individual disease progression in l-CBS and r-CBS single cases. CONCLUSIONS: For similar durations of disease, volumetric grey matter loss related to CBS pathology appeared earlier and progressed faster in l-CBS than in r-CBS. Cognitive impairment in r-CBS was characterized by apraxia, and additional memory and perceptional deficits for l-CBS.
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Enfermedades de los Ganglios Basales , Ganglios Basales , Sustancia Gris , Enfermedades Neurodegenerativas , Anciano , Ganglios Basales/patología , Ganglios Basales/fisiopatología , Enfermedades de los Ganglios Basales/patología , Enfermedades de los Ganglios Basales/fisiopatología , Estudios Transversales , Femenino , Estudios de Seguimiento , Sustancia Gris/patología , Sustancia Gris/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , SíndromeRESUMEN
Amyotrophic lateral sclerosis (ALS) is characterized by neuro-ophthalmological abnormalities beyond disturbed oculomotor control such as decreased visual acuity and disturbed visual evoked potentials. Here we report retinal alterations in a cohort of 24 patients with clinically definite (n = 20) or probable (n = 4) ALS as compared to matched controls. High-resolution spectral domain optical coherence tomography with retinal segmentation revealed a subtle reduction in the macular thickness and the retinal nerve fiber layer (RNFL) as well as a marked thinning of the inner nuclear layer (INL). Our data indicate an unprecedented retinal damage pattern and suggest neurodegeneration beyond the motor system in this disease.
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Expectation contributes to placebo and nocebo responses in Parkinson's disease (PD). While there is evidence for expectation-induced modulations of bradykinesia, little is known about the impact of expectation on resting tremor. Subthalamic nucleus (STN) deep brain stimulation (DBS) improves cardinal PD motor symptoms including tremor whereas impairment of verbal fluency (VF) has been observed as a potential side-effect. Here we investigated how expectation modulates the effect of STN-DBS on resting tremor and its interaction with VF. In a within-subject-design, expectation of 24 tremor-dominant PD patients regarding the impact of STN-DBS on motor symptoms was manipulated by verbal suggestions (positive [placebo], negative [nocebo], neutral [control]). Patients participated with (MedON) and without (MedOFF) antiparkinsonian medication. Resting tremor was recorded by accelerometry and bradykinesia of finger tapping and diadochokinesia were assessed by a 3D ultrasound motion detection system. VF was quantified by lexical and semantic tests. In a subgroup of patients, the effect of STN-DBS on tremor was modulated by expectation, i.e. tremor decreased (placebo response) or increased (nocebo response) by at least 10% as compared to the control condition while no significant effect was observed for the overall group. Interestingly, nocebo responders in MedON were additionally characterized by significant impairment in semantic verbal fluency. In contrast, bradykinesia was not affected by expectation. These results indicate that the therapeutic effect of STN-DBS on tremor can be modulated by expectation in a subgroup of patients and suggests that tremor is also among the parkinsonian symptoms responsive to placebo and nocebo interventions. While positive expectations enhanced the effect of STN-DBS by further decreasing the magnitude of tremor, negative expectations counteracted the therapeutic effect and at the same time exacerbated a side-effect often associated with STN-DBS. The present findings underscore the potency of patients' expectation and its relevance for therapeutic outcomes.
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Cognición , Estimulación Encefálica Profunda/psicología , Emociones , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Temblor/complicaciones , Anciano , Femenino , Humanos , Hipocinesia/complicaciones , Masculino , Persona de Mediana Edad , Actividad Motora , Efecto Nocebo , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Habla/fisiología , Núcleo Subtalámico/fisiopatología , Investigación Biomédica Traslacional , Resultado del TratamientoRESUMEN
Expectation contributes to placebo and nocebo responses in Parkinson's disease (PD). Subthalamic nucleus (STN) deep brain stimulation (DBS) improves proximal more than distal movements whereas it impairs executive cognitive function such as verbal fluency (VF). We investigated how expectation modulates the pattern of motor improvement in STN-DBS and its interaction with VF. In a within-subject-design, expectation of 24 hypokinetic-rigid PD patients regarding the impact of STN-DBS on motor symptoms was manipulated by verbal suggestions (positive [placebo], negative [nocebo], neutral [control]). Patients participated with (MedON) and without (MedOFF) antiparkinsonian medication. Motor function was assessed by Unified Parkinson's Disease Rating Scale and quantitative kinematic analysis of proximal alternating hand and distal finger tapping. VF was quantified by lexical and semantic tests. In MedOFF, expectation significantly affected proximal but not distal movements resulting in better performance in the placebo than in the nocebo condition. Placebo responders with improvement of ≥25% were characterized by a trend for impaired lexical VF. These results indicate that positive motor expectations exert both motor placebo and cognitive nocebo responses by further enhancing the STN-DBS-effect on proximal movements and by impairing VF. The placebo response on motor performance resembles the clinically known STN-DBS-effect with stronger improvement in proximal than distal movements. The nocebo response on VF is likely due to implicit learning mechanisms associated with an expectation-induced placebo response on motor performance.
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Trastornos del Conocimiento/terapia , Estimulación Encefálica Profunda/métodos , Estimulación Encefálica Profunda/psicología , Movimiento/fisiología , Enfermedad de Parkinson , Efecto Placebo , Adulto , Anciano , Trastornos del Conocimiento/etiología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/terapia , Desempeño Psicomotor , Índice de Severidad de la Enfermedad , Núcleo Subtalámico/fisiología , Encuestas y Cuestionarios , Aprendizaje VerbalRESUMEN
BACKGROUND: Anti-NMDA-encephalitis is caused by antibodies against the N-methyl-D-aspartate receptor (NMDAR) and characterized by a severe encephalopathy with psychosis, epileptic seizures and autonomic disturbances. It predominantly occurs in young women and is associated in 59% with an ovarian teratoma. RESULTS: We describe effects of cerebrospinal fluid (CSF) from an anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patient on in vitro neuronal network activity (ivNNA). In vitro NNA of dissociated primary rat cortical populations was recorded by the microelectrode array (MEA) system.The 23-year old patient was severely affected but showed an excellent recovery following multimodal immunomodulatory therapy and removal of an ovarian teratoma. Patient CSF (pCSF) taken during the initial weeks after disease onset suppressed global spike- and burst rates of ivNNA in contrast to pCSF sampled after clinical recovery and decrease of NMDAR antibody titers. The synchrony of pCSF-affected ivNNA remained unaltered during the course of the disease. CONCLUSION: Patient CSF directly suppresses global activity of neuronal networks recorded by the MEA system. In contrast, pCSF did not regulate the synchrony of ivNNA suggesting that NMDAR antibodies selectively regulate distinct parameters of ivNNA while sparing their functional connectivity. Thus, assessing ivNNA could represent a new technique to evaluate functional consequences of autoimmune encephalitis-related CSF changes.
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Anticuerpos/líquido cefalorraquídeo , Encefalitis/líquido cefalorraquídeo , Receptores de N-Metil-D-Aspartato/inmunología , Animales , Células Cultivadas , Corteza Cerebral/citología , Embrión de Mamíferos , Femenino , Humanos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo , Transfección , Adulto JovenRESUMEN
Parkinson's disease (PD) is associated with pathologically altered oscillatory activity. While synchronized oscillations between 13 and 30 Hz are increased within a cortico-subcortical network, cortico-muscular coupling (CMC) is decreased. The present study aims at investigating the effect of non-invasive transcranial alternating current stimulation (tACS) of the primary motor cortex (M1) on motor symptoms and motor-cortical oscillations in PD. In 10 PD patients and 10 healthy control subjects, static isometric contraction, dynamic fast finger tapping, and diadochokinesia of the more severely affected hand were investigated prior to and shortly after tACS of the contralateral M1 at 10 Hz vs. 20 Hz vs. sham. During isometric contraction, neuromagnetic activity was recorded using magnetoencephalography. 20 Hz tACS attenuated beta band CMC during isometric contraction and amplitude variability during finger tapping in PD patients but not in healthy control subjects. 10 Hz tACS yielded no significant after-effects. The present data suggest that PD is associated with pathophysiological alterations which abet a higher responsiveness toward frequency-specific tACS - possibly due to pathologically altered motor-cortical oscillatory synchronization at frequencies between 13 and 30 Hz.
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Feedback to both actively performed and observed behaviour allows adaptation of future actions. Positive feedback leads to increased activity of dopamine neurons in the substantia nigra, whereas dopamine neuron activity is decreased following negative feedback. Dopamine level reduction in unmedicated Parkinson's Disease patients has been shown to lead to a negative learning bias, i.e. enhanced learning from negative feedback. Recent findings suggest that the neural mechanisms of active and observational learning from feedback might differ, with the striatum playing a less prominent role in observational learning. Therefore, it was hypothesized that unmedicated Parkinson's Disease patients would show a negative learning bias only in active but not in observational learning. In a between-group design, 19 Parkinson's Disease patients and 40 healthy controls engaged in either an active or an observational probabilistic feedback-learning task. For both tasks, transfer phases aimed to assess the bias to learn better from positive or negative feedback. As expected, actively learning patients showed a negative learning bias, whereas controls learned better from positive feedback. In contrast, no difference between patients and controls emerged for observational learning, with both groups showing better learning from positive feedback. These findings add to neural models of reinforcement-learning by suggesting that dopamine-modulated input to the striatum plays a minor role in observational learning from feedback. Future research will have to elucidate the specific neural underpinnings of observational learning.
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Retroalimentación Psicológica , Aprendizaje , Enfermedad de Parkinson/psicología , Adulto , Anciano , Estudios de Casos y Controles , Cuerpo Estriado/fisiopatología , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Pruebas Psicológicas , Sustancia Negra/fisiopatologíaRESUMEN
BACKGROUND/OBJECTIVE: Corticobasal syndrome (CBS) is a rare neurodegenerative disorder characterized by a progressive and asymmetric manifestation of cortical and basal-ganglia symptoms of different origin. The spatio-temporal dynamics of cerebral atrophy in CBS is barely known. This study aimed to longitudinally quantify the individual dynamics of brain volume changes in patients with CBS as compared to healthy controls. METHODS: We used deformation-field-based morphometry (DFM) to study volumetric changes of each individual brain in short intervals of a few months. DFM enabled the quantitative analysis of local volume changes without predefining regions of interest in MR images of 6 patients with CBS and 11 matched healthy controls. A total of 64 whole brain 3D-MR-scans were acquired two to eight times over periods of 14 to 26 months. Based on repeated registrations of MR observations to the initial scan, maps of local volume ratio changes were computed. RESULTS: Compared to controls patients showed significant and increasing volume loss over time in premotor and primary-motor-cortices, somatosensory area 3a, superior parietal areas BA 5/7, and corticospinal tract. Furthermore, significant and asymmetric atrophy was identified in the caudate nucleus head, putamen, pallidum, motor-thalamus and substantia nigra. Temporal lobe was affected in those patients who presented progressive cognitive impairment. CONCLUSIONS: The analysis revealed localized, pathological changes in brains of patients with CBS, which differed significantly from those occurring during aging in healthy controls. As compared to age- and sex-matched controls, brains of CBS patients showed a common degenerating neural network comprising the motor circuit with basal ganglia and motor thalamic nuclei as well as the premotor and primary-motor-cortex.
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Encéfalo/patología , Enfermedades del Sistema Nervioso/patología , Análisis Espacio-Temporal , Anciano , Atrofia/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los ÓrganosRESUMEN
Schizophrenia is a chronic illness of heterogenous biological origin. We hypothesized that, similar to chronic progressive brain conditions, persistent functional disturbances of neurons would result in disturbed proteostasis in the brains of schizophrenia patients, leading to increased abundance of specific misfolded, insoluble proteins. Identification of such proteins would facilitate the elucidation of molecular processes underlying these devastating conditions. We therefore generated antibodies against pooled insoluble proteome of post-mortem brains from schizophrenia patients in order to identify unique, disease-specific epitopes. We successfully identified such an epitope to be present on collapsin-response mediator protein 1 (CRMP1) in biochemically purified, insoluble brain fractions. A genetic association analysis for the CRMP1 gene in a large Finnish population cohort (n = 4651) corroborated the association of physical and social anhedonia with the CRMP1 locus in a DISC1 (Disrupted-in-schizophrenia 1)-dependent manner. Physical and social anhedonia are heritable traits, present as chronic, negative symptoms of schizophrenia and severe major depression, thus constituting serious vulnerability factors for mental disease. Strikingly, lymphoblastoid cell lines derived from schizophrenia patients mirrored aberrant CRMP1 immunoreactivity by showing an increase of CRMP1 expression, suggesting its potential role as a blood-based diagnostic marker. CRMP1 is a novel candidate protein for schizophrenia traits at the intersection of the reelin and DISC1 pathways that directly and functionally interacts with DISC1. We demonstrate the impact of an interdisciplinary approach where the identification of a disease-associated epitope in post-mortem brains, powered by a genetic association study, is rapidly translated into a potential blood-based diagnostic marker.
Asunto(s)
Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteoma/metabolismo , Adulto , Animales , Encéfalo/metabolismo , Línea Celular Tumoral , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Genómica , Humanos , Ratones , Proteoma/genética , Proteómica , Proteína Reelina , Esquizofrenia/genética , Esquizofrenia/metabolismo , TransfecciónRESUMEN
BACKGROUND/OBJECTIVE: Parkinson's disease (PD) and the atypical parkinsonian syndromes multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are movement disorders associated with degeneration of the central nervous system. Degeneration of the retina has not been systematically compared in these diseases. METHODS: This cross-sectional study used spectral-domain optical coherence tomography with manual segmentation to measure the peripapillar nerve fiber layer, the macular thickness, and the thickness of all retinal layers in foveal scans of 40 patients with PD, 19 with MSA, 10 with CBS, 15 with PSP, and 35 age- and sex-matched controls. RESULTS: The mean paramacular thickness and volume were reduced in PSP while the mean RNFL did not differ significantly between groups. In PSP patients, the complex of retinal ganglion cell- and inner plexiform layer and the outer nuclear layer was reduced. In PD, the inner nuclear layer was thicker than in controls, MSA and PSP. Using the ratio between the outer nuclear layer and the outer plexiform layer with a cut-off at 3.1 and the additional constraint that the inner nuclear layer be under 46 µm, we were able to differentiate PSP from PD in our patient sample with a sensitivity of 96% and a specificity of 70%. CONCLUSION: Different parkinsonian syndromes are associated with distinct changes in retinal morphology. These findings may serve to facilitate the differential diagnosis of parkinsonian syndromes and give insight into the degenerative processes of patients with atypical parkinsonian syndromes.